It is known that both genetic and environmental determinants contribute to the expression of allergic disease, but precise gene-environment interactions have not been well-characterized. African Americans as a group suffer greater morbidity and mortality due to asthma than the general population, and an important risk factor is cockroach sensitization. A common argument is that African Americans, who are disproportionately represented in the lower socioeconomic strata, are subjected to greater cockroach allergen exposure as an effect of cockroach infestation; however, the susceptibility to cockroach sensitization persists even after adjusting for income. Consequently, we believe that there may be distinct genes, which, unlike 'asthma susceptibility' genes, confer an added risk for asthma and/or asthma severity in cockroach-allergic African Americans. The overall objective of our proposal is to search for MHC and non-MHC allelic variants in 5q31, 12q12, and 17ql 1 that are unique for asthmatics who demonstrate a specific immune response to cockroach. Our approach is to genotype a well-characterized cohort which is part of the NIH-funded 'Airway Disease and Cockroach Exposure in Public Housing' study (Togias, PI). Significant findings will be replicated in two independent groups of asthma families participating in the NIH studies 'Inner City Cockroach Allergen Reduction Trial' (Eggleston, PI) and the Collaborative Study on the Genetics of Asthma (Beaty, PI). Thus, our proposal builds upon a unique database where the opportunity exists to investigate the immunogenetics of a distinct and well-defined phenotype. We will also examine the interactive effect of current cockroach allergen exposure and susceptibility loci associated with asthma severity.